crossing96/oncoscreening huggingface dataset:
Downregulation of pigment epithelium-derived factor is associated with increased epithelial-mesenchymal transition in bladder cancer.	BACKGROUND: Pigment epithelium-derived factor (PEDF) has been reported to inhibit angiogenesis in bladder cancer, but whether it modulates epithelial-mesenchymal transition (EMT) remains unknown. METHODS: We have included 68 samples of non-muscle invasive bladder cancer in this study. Immunohistochemistry was performed in all sample sections for expressions of PEDF, SNAI2, Vimentin and E-cadherin, which were quantified and The EMT Index (EMTi) was calculated by Vimentin/E-cadherin. Levels of expression were studied for correlations with clinicopathological parameters. RESULTS: Patients were grouped with high (EMTi≤1) and low (EMTi>1) EMT level for comparisons of clinicopathological parameters. In the univariate analysis, EMT level was shown to be significantly associated with tumor onset and PEDF level, but not with gender, occurrence, stage, grade, or SNAI2 level. Further multivariate analysis revealed that PEDF level was significantly negatively correlated with EMTi independent of other clinicopathological parameters. CONCLUSIONS: Our results indicate that PEDF may serve as a promising novel modality for the treatment of bladder cancer, as it can inhibit not only angiogenesis but also EMT process of bladder cancer.	bladder
The efficacy of BCG TICE and BCG Connaught in a cohort of 2,099 patients with T1G3 non-muscle-invasive bladder cancer.	BACKGROUND: Potential differences in efficacy of different bacillus Calmette-Guérin (BCG) strains are of importance for daily practice, especially in the era of BCG shortage. OBJECTIVE: To retrospectively compare the outcome with BCG Connaught and BCG TICE in a large study cohort of pT1 high-grade non-muscle-invasive bladder cancer patients. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data were collected for 2,451 patients with primary T1G3 tumors from 23 centers who were treated with BCG for the first time between 1990 and 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using Cox multivariable regression and adjusting for the most important prognostic factors in this nonrandomized comparison, BCG Connaught and TICE were compared for time to recurrence, progression, and the duration of cancer specific survival and overall survival. RESULTS AND LIMITATIONS: Information on the BCG strain was available for 2,099 patients: 957 on Connaught and 1,142 on TICE. Overall, 765 (36%) patients received some form of maintenance BCG, 560 (59%) on Connaught and 205 (18%) on TICE. Without maintenance, Connaught was more effective than TICE only for the time to first recurrence (hazard ratio [HR] = 1.48; 95% CI: 1.20-1.82; P<0.001). With maintenance, TICE was more effective than Connaught for the time to first recurrence (HR = 0.66; 95% CI: 0.47-0.93; P = 0.019) with a trend for cancer specific survival (HR = 0.36; 95% CI: 0.14-0.92; P = 0.033). For time to progression and overall survival, Connaught and TICE had a similar efficacy. Compared to no maintenance therapy, maintenance BCG significantly reduced the risk of recurrence, progression and death, both overall, and disease specific, for TICE, but not for Connaught. CONCLUSIONS: We found that BCG Connaught results in a lower recurrence rate as compared with BCG TICE when no maintenance is used. However, the opposite is true when maintenance is given. PATIENT SUMMARY: As there is currently a BCG shortage, information on the efficacy of different BCG strains is important. In this nonrandomized retrospective comparison in over 2,000 patients, we found that BCG Connaught reduces the recurrence rate compared to BCG TICE when no maintenance is used, but the opposite is true when maintenance is given.	bladder
Lentivirus-mediated p21/Waf-1 short hairpin RNA enhances the cytotoxic effects and replicative potential of a bladder cancer-specific oncolytic adenovirus in vitro.	Our previous work confirmed that the bladder cancer-specific oncolytic adenovirus Ad/PSCAE/UPII/E1A could selectively replicate in bladder cancer cells, thus causing specific tumor cell lysis. The replicative potential is a crucial factor in determining the therapeutic efficacy of oncolytic adenoviruses. However, viral replication is attenuated by the low-activity promoter that we used, thus compromising viral cytotoxicity. In this study, we investigated the effect of the cell cycle-dependent kinase inhibitor p21/Waf-1 on an adenovirus. We used lentivirus-mediated short hairpin RNA to knock down p21/Waf-1 in two bladder cancer cell lines EJ and 5637. The p21/Waf-1 knockdown not only induced stronger cytopathic effects but also augmented apoptosis, which was closely associated with the enhancement of Fas and the subsequent significant activation of caspase-3. A replicative assay showed that p21/Waf-1 knockdown increased the viral particle production. Western blot analysis confirmed that p21/Waf-1 knockdown upregulated the expression of androgen receptor (AR) and two adenovirus replication indicators E1A and hexon. A luciferase activity assay indicated higher transcriptional activity of the uroplakin II (UPII) promoter in the p21/Waf-1 knockdown cells, and one possible mechanism could be that the increased expression of AR induced the UPII promoter through the AR-binding sites of the prostate stem cell antigen enhancer. These findings indicating that p21/Waf-1 knockdown could enhance cell killing and viral replication have significant implications for the development of bladder cancer-specific oncolytic adenovirus therapies.	bladder
Precise positioning of cancerous cells on PDMS substrates with gradients of elasticity.	In this work the novel method to create PDMS substrates with continuous and discrete elasticity gradients of different shapes and dimensions over the large areas was introduced. Elastic properties of the sample were traced using force spectroscopy (FS) and quantitative imaging (QI) mode of atomic force microscopy (AFM). Then, fluorescence microscopy was applied to investigate the effect of elastic properties on proliferation of bladder cancer cells (HCV29). Obtained results show that cancerous cells proliferate significantly more effective on soft PDMS, whereas the stiff one is almost cell-repellant. This strong impact of substrate elasticity on cellular behavior is driving force enabling precise positioning of cells.	bladder
Biocompatible astaxanthin as novel contrast agent for biomedical imaging.	Photoacoustic imaging (PAI) is a hybrid imaging modality with high resolution and sensitivity that can be beneficial for cancer staging. Due to insufficient endogenous photoacoustic (PA) contrast, the development of exogenous agents is critical in targeting cancerous tumors. The current study demonstrates the feasibility of marine-oriented material, astaxanthin, as a biocompatible PA contrast agent. Both silicon tubing phantoms and ex vivo bladder tissues are tested at various concentrations (up to 5 mg/ml) of astaxanthin to quantitatively explore variations in PA responses. A Q-switched Nd : YAG laser (λ = 532 nm) in conjunction with a 5 MHz ultrasound transducer is employed to generate and acquire PA signals from the samples. The phantom results presented that the PA signal amplitudes increase linearly with the astaxanthin concentrations (threshold detection = 0.31 mg/ml). The tissue injected with astaxanthin yields up to 16-fold higher PA signals, compared with that with saline. Due to distribution of the injected astaxanthin, PAI can image the margin of astaxanthin boles as well as quantify their volume in 3D reconstruction. Further investigations on selective tumor targeting are required to validate astaxanthin as a potential biocompatible contrast agent for PAI-assisted bladder cancer detection.	bladder
Failure of Bacillus Calmette-Guérin therapy in non-muscle-invasive bladder cancer: Definition and treatment options.	"Adjuvant intravesical bacillus Calmette- Guérin (BCG) therapy is the standard conservative adjuvant treatment and the most effective regimen for patients with high-risk non-muscle-invasive bladder cancer (NMIBC). The term ""BCG failure"" is generally used to refer to recurrence or progression following BCG therapy, as experienced by many patients. However, the term has been defined inconsistently, and several studies have indicated that patients with a particular pattern of BCG failure have a worse prognosis. There are many different treatment options for patients who experience BCG failure. OBJECTIVE: To summarize the different current definitions of BCG failure and the present treatment options available for patients with high-risk NMIBC who experience BCG failure. EVIDENCE SYNTHESIS: Overall, the failure rate in response to BCG is about 40-50%. Most guidelines recommend that patients failing BCG should be offered radical cystectomy (RC). The significant potential for progression specific to high-risk NMIBC leads some clinicians to argue that immediate RC should be considered the preferred first-line treatment in high-risk patients, bearing in mind that it achieves a long-term survival rate in excess of 90% with ongoing improvements in morbidity. While other salvage intravesical treatments have to be considered oncologically inferior to RC, several therapies are now available if the patient is unfit to undergo RC or if bladder preservation is the objective, and some agents have shown promise in the context of BCG failure. CONCLUSIONS: The definition, prediction, and treatment of BCG failure remain topics of debate. Patients with BCG failure need carefully selected, individualized therapy in experienced hands. Stratification of patients with BCG failure into groups can identify those with a better or worse prognosis. RC should be the selected option if a patient experiences BCG failure, but several promising intravesical salvage options are available for those cases in which the patient is unfit for surgery or bladder preservation is preferred. Currently data are still inadequate to allow formulation of definitive recommendations, and larger and higher quality studies of salvage intravesical therapies are urgently required."	bladder
The neutrophil-to-lymphocyte ratio as a predictor of intravesical recurrence in patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy.	BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation associated with recurrence and poor prognosis in numerous cancer types. The aim of this study was to evaluate the use of the NLR as a biomarker for intravesical recurrence (IVR) in patients undergoing radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC) for the first time. METHODS: We retrospectively analyzed the records of 100 patients with UTUC who had undergone RNU between 1999 and 2015 at our institution. The association between the preoperative NLR and IVR were assessed using multivariate models. RESULTS: Among the 100 patients enrolled in the study, 33 developed IVR during a median follow-up of 34 months. The receiver operating characteristic analysis revealed that the optimum cut-off value for the preoperative NLR was >3.8. A high preoperative NLR (n = 21) was associated with a significantly increased risk of lymph node involvement (p = 0.036) and IVR (p = 0.034) compared with a low preoperative NLR (n = 79). IVR-free survival in patients with a high preoperative NLR was significantly worse than that of patients with a low preoperative NLR (p = 0.018). On multivariate analysis, the preoperative NLR [hazard ratio (HR) 2.49; p = 0.015] and tumor multifocality (HR 2.96; p = 0.024) were independent risk factors predictive of IVR. CONCLUSION: In our study population of patients with UTUC who had undergone RNU the preoperative NLR was associated with a significantly increased risk of IVR, suggesting that the NRL could be a useful biomarker for predicting IVR.	bladder
Detection of multiple mutations in urinary exfoliated cells from male bladder cancer patients at diagnosis and during follow-up.	Most bladder cancer (BC) patients need life-long, invasive and expensive monitoring and treatment, making it a serious burden on the health system. Thus, there is a pressing need for an accurate test to assist diagnosis and surveillance of BC as an alternative to cystoscopy. Mutations in human TERT, FGFR3, PIK3CA, and RAS genes have been proposed as potential molecular markers in bladder tumor. Their concomitant presence in urine samples has not been fully explored.We investigated a panel of mutations in DNA from exfoliated urinary cells of 255 BC patients at diagnosis. Forty-one mutations in TERT, FGFR3, PIK3CA, and RAS were analyzed by SNaPshot assay in relation to clinical outcome. In 81 of these patients under surveillance, the same set of mutations was screened in additional 324 samples prospectively collected.The most common mutations detected in urine at diagnosis were in the TERT promoter. In non-invasive BC, these mutations were related to high risk and grade (p<0.0001) as well as progression to muscle-invasive disease (p=0.01), whereas FGFR3 mutations were observed in low-grade BC (p=0.02) and patients with recurrences (p=0.05). Stronger associations were observed for combined TERT and FGFR3 mutations and number of recurrences (OR: 4.54 95% CI: 1.23-16.79, p=0.02). Analyses of the area under the curve for combinations of mutations detected at diagnosis and follow-up showed an accuracy of prediction of recurrence of 0.80 (95% CI: 0.71-0.89).Mutations in urine of BC patients may represent reliable biomarkers. In particular, TERT and FGFR3 mutations have a good accuracy of recurrence prediction.	bladder
Vesigenurtacel-L (HS-410) in the management of high-grade nonmuscle invasive bladder cancer.	Unlike other malignancies, the death rate of bladder cancer has not declined in several decades, highlighting the need for new treatment options. In the emerging era of immunotherapy, therapeutic cancer vaccines are an attractive option to cure, control and prevent cancer. Despite this, finding a feasible and efficacious vaccine platform has proven elusive across all malignancies. Vesigenurtacel-L is the first whole cell, allogeneic vaccine intended to treat high-grade, nonmuscle invasive bladder cancer. This type of vaccine technology for bladder cancer is novel, and has the potential to be both economically and logistically feasible.	bladder
Use of sigmoid colon in orthotopic neobladder reconstruction: Long-term results.	OBJECTIVES: To present our experience with a sigmoid orthotopic neobladder. METHODS: We retrospectively evaluated the functional and oncological outcomes of 160 patients who underwent orthotopic neobladder reconstruction using a detubularized 20-25-cm sigmoid segment at our institution. Each patient was evaluated every 3 months the first year, every 6 months for the next 4 years and annually thereafter. Urodynamic studies of all consenting patients were carried out after 6 months, and 2, 5 and 10 years. We carried out the log-rank test, and used Cox regression models and Kaplan-Meier survival analysis. The anova test was used to compare urodynamic findings over time. RESULTS: Mean follow up was 6.8 years (range 0.65-21.7 years). Overall survival was 58.1% at 5 years, and 47.1% at 10 years. Early complications occurred in 36 patients (22.6%); late complications in 40 (25%). Stage V chronic kidney disease developed in two patients (1.3%). Complete (daytime and night-time) continence, defined as no need for pads or condom devices, was achieved by 45% of patients at 5 years, daytime continence was achieved by just 36% of patients; both were unchanged at 10 years. A significant difference emerged in maximal neobladder capacity and post-void residual values between 6 months and 2 years, and between 2 and 5 years (P < 0.01 and P = 0.03, respectively). CONCLUSIONS: Sigmoid neobladder continence and capacity significantly improve over the first 5 years, and they remain stable over the long term. Upper urinary tract function is not affected by endoluminal pressure, and the rate of metabolic imbalance is negligible.	bladder
Quantitative CT texture analysis for evaluating histologic grade of urothelial carcinoma.	PURPOSE: To investigate the feasibility of using CT texture analysis (CTTA) to differentiate between low- versus high-grade urothelial carcinoma. METHODS: A total of 105 patients with high-grade urothelial carcinoma (HGUC, n = 106) and low-grade urothelial carcinoma (LGUC, n = 18) were included in this retrospective study. Both unenhanced and enhanced CT images representing the largest cross-sectional area of the tumor were chosen for CTTA performed using TexRAD software. Comparison of texture parameters, mean gray-level intensity (Mean), standard deviation, entropy, mean of positive pixels (MPP), skewness, and kurtosis were made for the objective. Receiver operating characteristic (ROC) analysis was performed and the area under the ROC curve was calculated for texture parameters that were significantly different (P < 0.05) for the purpose. Sensitivity (Se), specificity (Sp), positive predictive value, negative predictive value, and accuracy were calculated using the cut-off value of texture parameter with the highest AUC. RESULTS: Compared to HGUC, LGUC had significantly lower Mean (P = 0.001), Entropy (P = 0.002), and MPP (P < 0.001) on unenhanced and enhanced images and lower SD (P = 0.048) on enhanced images. There was no significant difference in skewness or kurtosis at any texture scale on unenhanced and enhanced images. A MPP <24.13 at fine texture scale on unenhanced images identified LGUC from HGUC with the highest AUC of 0.779 ± 0.065 (Se = 72.2%, Sp = 84.9%, PPV = 44.8%, NPV = 94.7%, and accuracy = 83.1%). CONCLUSIONS: CTTA proved to be a feasible tool for differentiating LGUC from HGUC. MPP quantified from fine texture scale on unenhanced images was the optimal diagnostic parameter for estimating histologic grade of urothelial carcinoma.	bladder
Effect of combined treatment of radiation and tissue-specific recombinant oncolytic adenovirus on bladder cancer cells.	PURPOSE: Gene therapy combined with radiation has shown promising potential for the treatment of tumors. This paper aimed to clarify the synergistic effect of radiotherapy combined with the bladder cancer tissue-specific oncolytic adenovirus (Ad-PSCAE-UPII-E1A) on bladder cancer cells and to study the underlying synergy mechanisms of the combined treatment. MATERIALS AND METHODS: The Adenovirus carrying E1A under control of UPII promoter and prostate stem cell antigen enhancer (PSCAE) were successfully constructed. The viability of bladder cancer cells BIU-87 and EJ was determined by MTT assay. The apoptotic assay was demonstrated by flow cytometry and TEM. Virus titer was determined by TCID50 assay, and proteins Mre11, Chk2-Thr68, and E1A were analyzed by Western blot method. RESULTS: Oncolytic adenovirus combined with radiotherapy improved antitumor efficacy compared with the single treatment at a time and was X-ray dosage-dependent. When the adenovirus infection was scheduled at 24 h after irradiation, cancer cells had the lowest viability. Adenovirus and irradiation induced cell death through the caspase-3 related apoptotic pathway, and bladder cancer cells were arrested at the G1 (BIU-87) or S phase (EJ). Autophagic vacuoles were observed in bladder cancer cells treated with radiation and adenovirus. After irradiation, more virus particles were observed in the BIU-87 and EJ cells. However, by a TCID50 assay, there was no difference in virus titter between irradiated bladder cancer cells and unirradiated cells. The proteins Mre11, Chk2-Thr68 which involved in the DNA break repair pathway were decreased while γ-H2AX-Ser139 increased; at the same time, the E1A gene and the hexon proteins of oncolytic adenovirus were increased after irradiation. CONCLUSIONS: Our results proved synergistic antitumor effect of adenovirus Ad-PSCAE-UPII-E1A and radiation, which might be a potential therapeutic strategy for bladder cancer.	bladder
Synthesis of novel arylaminoquinazolinylurea derivatives and their antiproliferative activities against bladder cancer cell line.	A novel series of arylurea and arylamide derivatives 1a-z, 2a-d having aminoquinazoline scaffold was designed and synthesized. Their in vitro antiproliferative activities against RT112 bladder cancer cell line and inhibitory activities against FGFR3 kinase were tested. Most compounds showed good antiproliferative activities against RT112 bladder cancer cell line, and arylurea compounds 1a-z were more potent than arylamide compounds 2a-d. Among them, eight compounds 1a, 1d-g, 1l, 1y, and 1z showed potent activities with GI(50) values below submicromolar range. Especially, arylurea compounds 1d and 1g possessing 2,3-dimethyl and 3,4-dimethyl moieties exhibited superior or similar antiproliferative activity (GI(50)=8.8nM and 30.2nM, respectively) to AZD4547 (GI(50)=29.2nM) as a reference standard.	bladder
An Epigenomic Approach to Improving Response to Neoadjuvant Cisplatin Chemotherapy in Bladder Cancer.	Bladder cancer is among the five most common cancers diagnosed in the Western world and causes significant mortality and morbidity rates in affected patients. Therapeutic options to treat the disease in advanced muscle-invasive bladder cancer (MIBC) include cystectomy and chemotherapy. Neoadjuvant cisplatin-based combination chemotherapy is effective in MIBC; however, it has not been widely adopted by the community. One reason is that many patients do not respond to neoadjuvant chemotherapy, and no biomarker currently exists to identify these patients. It is also not clear whether a strategy to sensitize chemoresistant patients may exist. We sought to identify cisplatin-resistance patterns in preclinical models of bladder cancer, and test whether treatment with the epigenetic modifier decitabine is able to sensitize cisplatin-resistant bladder cancer cell lines. Using a screening approach in cisplatin-resistant bladder cancer cell lines, we identified dysregulated genes by RNA sequencing (RNAseq) and DNA methylation assays. DNA methylation analysis of tumors from 18 patients receiving cisplatin-based chemotherapy was used to confirm in vitro results. Cisplatin-resistant bladder cancer cells were treated with decitabine to investigate epigenetic sensitization of resistant cell lines. Our results show that HOXA9 promoter methylation status is associated with response to cisplatin-based chemotherapy in bladder cancer cell lines and in metastatic bladder cancer. Bladder cancer cells resistant to cisplatin chemotherapy can be sensitized to cisplatin by the DNA methylation inhibitor decitabine. Our data suggest that HOXA9 promoter methylation could serve as potential predictive biomarker and decitabine might sensitize resistant tumors in patients receiving cisplatin-based chemotherapy.	bladder